Update Evenity followed by 2 years of alendronate

I had the same issue when seeking bhrt. I went to a functional medicine provider.

@gravity3
I will try to find one. In full disclosure my husband is a retired Internal
medicine doc. I also saw an integrative endocrinologist and i have a regular endocrinologist. All 3 said no. My gains were so good on Evenity their thinking was risk vs benefit. Don’t get too greedy!! Now look where I am. I am beyond frustrated and worried. I have bunion surgery coming up Nov 14 which will put me a bit immobile for a while and I’m not sure I can afford that right now. Waiting on
my CTX. Just freaking out massively.

hikernurse,

I’m sorry to hear about the unanticipated BMD loss while on Fosamax. A CTX of 361 with the accompanying BMD loss suggests your bone turnover isn’t fully suppressed. If you could, please share what your CTX shows when your new labs come back.

While switching to a stronger antiresorptive such as zoledronic acid or Prolia would likely be recommended, in your situation I’d lean more toward an anabolic. With the upcoming bunion surgery and a modest turnover state, a course of Tymlos or Forteo could help re-stimulate bone formation and protect against the BMD loss that often happens during periods of reduced mobility.

Starting Tymlos or Forteo would also give you a period of time to think over the next step - which antiresorptive to use afterward to protect the gains. This would also open the door for another round of Evenity should you need it.

@mayblin
Thank you so much for your kind guidance Malin my husband who is a retired MD wholeheartedly agrees with you so I believe I will try to contact my endocrinologist through the portal and try to get it started ASAP. My concern is the upcoming surgery and I’d like to have something on board that is helping me with my bones and through that period of immobility many many thanks. I guess I don’t understand why the eluate held my gains and even increase them for a year but in the second year they did not and this is a true test to why you get a DEXA every year and not every two years I basically had to beg for one every year, and I would encourage everybody to push for that thank you

@mayblin
I am confused by your use of the term 'bone turnover rate.' I had thought 'turnover' included both removal of old bone and formation of new bone.

Why would 'fully' suppressing 'bone turnover' be a good thing?

@rjd Agreed - "fully suppressing bone turnover" doesn't make sense. The bone remodeling process includes breakdown and rebuilding. You want good turnover, and you don't want the breakdown process to be greater than the rebuilding process.

@rjd

That’s an excellent point. The foundation of healthy adult bone lies in balanced remodeling - the removal of old or damaged bone and the formation of new bone, as you mentioned.

However, bisphosphonates act selectively on osteoclasts to reduce bone resorption. Because bone formation is coupled to resorption, osteoblast activity also decreases secondarily, leading to an overall reduction of bone turnover. The end result, unfortunately, isn’t a perfectly balanced turnover - far from it. I’d also like to add that a CTX of 361 in an untreated person would probably be considered appropriate, provided there is adequate osteoblast activity.

At present, there’s no precise way to fine-tune these agents to maintain an ideal level of bone turnover, or balanced resorption and formation. The therapeutical goal is to suppress remodeling enough to reduce fracture risk and preserve bone mass, without over-suppression (which might necessitate drug holidays or dosing adjustments). In hindsight, my earlier wording “fully suppressed” would have been better expressed as “sufficiently suppressed.”

That’s my understanding, and I’d love to hear your or anyone else’s thoughts on it.

I am unaware that osteoblasts take some sort of cues from osteoclastic activity.

My rather simplistic understanding of why osteroporosis occurs is that post-menopausal women produce significantly reduced estrogen, which is the main engine driving osteoblastic (bone-building) activity. Meanwhile, osteoclasts continue unimpeded and outperform osteoblasts; the result is a loss of bone density because bone resorption outruns bone formation.

I simply do not understand the logic of suppressing 'remodeling' and that that might somehow lead to reducing fracture risk. You might preserve bone mass but is it of sufficient quality to prevent fractures?

In his book, McCormick likes CTX in the range 100-375 and P1NP in the range of 30-50.

@rjd
Yes, osteoblasts do take cues from osteoclast activity via “coupled remodeling.” When osteoclasts resorb bone, they release signals that help recruit and activate osteoblasts to rebuild at the same site. This process ensures that bone formation is closely linked to bone resorption, maintaining skeletal integrity:
https://pmc.ncbi.nlm.nih.gov/articles/PMC3899560/
You summarized postmenopausal bone loss due to estrogen deficiency really well. From what I’ve read, estrogen seems to act more as a regulator that maintains the balance between bone formation and resorption, rather than as a direct “engine” driving osteoblast activity.

I share your skepticism about fracture reduction resulting from suppressing remodeling by bisphosphonates. Clinical trials have, however, shown a reduction in fracture risk, especially in the first 3–5 years, likely because bisphosphonates preserve existing trabecular connectivity and slow the rate of resorption, hence helping maintain bone density. With available anabolic therapies nowadays, the approach of repeated use of an anabolic agent followed by antiresorptive therapy is now evidence-based, increasingly recommended, and reflected in some updated clinical guidelines. Hopefully, this represents a better long-term management strategy.

I reviewed briefly the cited source and it is way beyond my pay grade. However, my takeaway is that there are many sources of the 'cues' given to guide osteoblasts to go where they are needed.

The term 'coupled remodeling' should suggest only that osteoblast receive some sort of guidance on where to go NOT who/what issues that guidance.

Clearly some sort of 'coupling' is required for successful remodeling but how that is accomplished looks to be still at a theoretical stage. So it is not at all clear to me that bisphosphonates, which force into hibernation some part of osteoclastic activity, thereby also reduce osteoblast efforts.

I feel like I am missing something but have no idea what that might be.